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Gilles Russ Thyroid and Endocrine Tumor Unit, Department of Nuclear Medicine, Pitié Salpêtrière Hospital, University Pierre et Marie Curie, Paris, France

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Sophie Leboulleux Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, University Paris-Sud, Villejuif, France

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Laurence Leenhardt Thyroid and Endocrine Tumor Unit, Department of Nuclear Medicine, Pitié Salpêtrière Hospital, University Pierre et Marie Curie, Paris, France

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Laszlo Hegedüs Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

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A thyroid incidentaloma is an unexpected, asymptomatic thyroid tumor fortuitously discovered during the investigation of an unrelated condition. The prevalence rate is 67% with ultrasonography (US) imaging, 15% with computed tomography (CT) or magnetic resonance imaging (MRI) of the neck, and 1-2% with fluorodeoxyglucose (FDG) positron emission tomography. In the absence of a history of external beam radiation or familial medullary thyroid cancer, the risk of malignancy ranges between 5 and 13% when discovered with US, CT or MRI, but is much higher if based on focal FDG uptake (30%). All patients with a thyroid incidentaloma, independent of the mode of detection, should undergo a dedicated neck US with risk stratification: US imaging allows a quantitative risk stratification of malignancy in thyroid nodules, named ‘reporting system' or ‘TIRADS' (thyroid imaging reporting and data system). The reported sensitivity ranges from 87 to 95% for the detection of carcinomas and the negative predictive value from 88 to 99.8%. We suggest that the indications for fine-needle aspiration be based mainly on size and US risk stratification. However, the diagnosis and workup of thyroid incidentalomas leads to superfluous surgery for benign conditions, and excess diagnosis and treatment of papillary microcarcinomas, the vast majority of which would cause no harm. Recognizing this must form the basis of any decision as to supplementary investigations and whether to offer therapy, in a close dialogue between patient and physician. The current use of minimally invasive nonsurgical ablation options, as alternatives to surgery, is highlighted.

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Clotilde Saïe Thyroid and Endocrine Tumors Unit, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Cécile Ghander Thyroid and Endocrine Tumors Unit, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Samir Saheb Apheresis Unit, Pitié-Salpêtrière Hospital, AP-HP, Sorbonne University, Paris, France

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Christel Jublanc Department of Endocrinology, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Denis Lemesle Department of Anaesthesia, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Charlotte Lussey-Lepoutre Nuclear Medicine Department, Pitié-Salpêtrière Hospital APHP, Sorbonne Université, Inserm U970, Paris, France

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Laurence Leenhardt Thyroid and Endocrine Tumors Unit, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Fabrice Menegaux Department of Surgery, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Christophe Tresallet Department of Surgery, Avicennes Hospital, Paris, France

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Camille Buffet Thyroid and Endocrine Tumors Unit, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Introduction: Hyperthyroid patients who are unresponsive to medical treatment remain a challenging clinical problem. Objective: The goal of our study was to evaluate the use of therapeutic plasma exchange (TPE) in hyperthyroid patients and their outcome after TPE. Method: We retrospectively reviewed 22 patients who underwent TPE for refractory thyrotoxicosis in our institution: 13 with Graves’ disease, 7 with amiodarone-induced thyrotoxicosis (AIT), 1 with toxic goiter, and 1 pregnant patient with familial nonautoimmune thyrotoxicosis. Results: Before TPE, all patients had severe hyperthyroidism, and antithyroid drugs were either contraindicated or not sufficiently effective to restore euthyroidism promptly. After all the TPEs, free T<sub>4</sub> (fT4) decreased significantly by 48% (p = 0.001) and fT3 by 52% (p = 0.0001). The median number of TPE sessions per patient was 4 (range: 1–10). There were no complications during the 91 TPE sessions. Total thyroidectomy with no severe side effects was performed on 16/22 patients and 1 other patient was treated with radioactive iodine. One patient died from severe thyrotoxicosis during medical care. The remaining 4 patients were followed up without any radical treatment. For all 7 patients with AIT, iterative TPE led to a significant clinical improvement, and amiodarone was continued for 1 patient. Available treatments were continued between TPE sessions (cholestyramine for 13 patients [60%] and glucocorticoids for 16 patients [73%]). Conclusion: TPE allowed a safe decrease of 50% in thyroid hormone levels, and it should be considered for refractory hyperthyroid patients when medical treatments are contraindicated or have failed to restore euthyroidism, irrespective of the etiology of the thyrotoxicosis.

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Gilles Russ Thyroid and Endocrine Tumors, Institute of Endocrinology, Pitié Salpêtrière Hospital, Pierre and Marie Curie University, Paris, France

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Steen J. Bonnema Department of Endocrinology, Odense University Hospital, Odense, Denmark

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Murat Faik Erdogan Department of Endocrinology and Metabolism, University of Ankara School of Medicine, İbni Sina Hastanesi, Ankara, Turkey

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Cosimo Durante Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy

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Rose Ngu Head Neck and Thyroid Imaging, Department of Radiology, Guy’s and St Thomas’ Hospitals NHS Foundation Trust, London, United Kingdom

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Laurence Leenhardt Thyroid and Endocrine Tumors, Institute of Endocrinology, Pitié Salpêtrière Hospital, Pierre and Marie Curie University, Paris, France

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Thyroid ultrasound (US) is a key examination for the management of thyroid nodules. Thyroid US is easily accessible, noninvasive, and cost-effective, and is a mandatory step in the workup of thyroid nodules. The main disadvantage of the method is that it is operator dependent. Thyroid US assessment of the risk of malignancy is crucial in patients with nodules, in order to select those who should have a fine needle aspiration (FNA) biopsy performed. Due to the pivotal role of thyroid US in the management of patients with nodules, the European Thyroid Association convened a panel of international experts to set up European guidelines on US risk stratification of thyroid nodules. Based on a review of the literature and on the American Association of Clinical Endocrinologists, American Thyroid Association, and Korean guidelines, the panel created the novel European Thyroid Imaging and Reporting Data System, called EU-TIRADS. This comprises a thyroid US lexicon; a standardized report; definitions of benign and low-, intermediate-, and high-risk nodules, with the estimated risks of malignancy in each category; and indications for FNA. Illustrated by numerous US images, the EU-TIRADS aims to serve physicians in their clinical practice, to enhance the interobserver reproducibility of descriptions, and to simplify communication of the results.

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George J. Kahaly Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

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Luigi Bartalena Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Lazlo Hegedüs Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

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Laurence Leenhardt Thyroid and Endocrine Tumors Unit, Pitié Salpêtrière Hospital, Sorbonne University, Paris, France

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Kris Poppe Endocrine Unit, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium

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Simon H. Pearce Department of Endocrinology, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom

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Graves’ disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves’ hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves’ hyperthyroidism are usually medically treated for 12–18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12–18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves’ patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves’ patients with mild/active orbitopathy receiving RAI.

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Martina Tavarelli Unité Thyroïde Tumeurs Endocrines, Paris, France

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Julie Sarfati Unité Thyroïde Tumeurs Endocrines, Paris, France

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Christian De Gennes Service de Médecine Interne Immuno-clinique, Paris, France

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Julien Haroche Service de Médecine Interne 2, Paris, France

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Camille Buffet Unité Thyroïde Tumeurs Endocrines, Paris, France

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Cécile Ghander Unité Thyroïde Tumeurs Endocrines, Paris, France

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Jean Marc Simon Service de Radiothérapie, Paris, France

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Fabrice Ménégaux Service de Chirurgie Générale et Digestive, Groupe Hospitalier et Faculté de Médecine Pitié-Salpêtrière, Institut du Cancer, Université Pierre et Marie Curie, Paris, France

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Laurence Leenhardt Unité Thyroïde Tumeurs Endocrines, Paris, France

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Background: Hypertrophic osteoarthropathy (HOA) is a rare condition characterized by bone and joint pain and digital clubbing usually associated with bronchopulmonary diseases. Primary HOA is rare and the pathogenesis remains unclear. Objectives: Cases of HOA as a paraneoplastic syndrome associated with thyroid carcinoma are very rare - only 2 cases have been described in the literature. Results: We present the first case of a 40-year-old patient affected by HOA associated with invasive differentiated follicular thyroid carcinoma operated in 2 stages. Both operations were followed by radioiodine ablation, and then a rapid unresectable local recurrence developed requiring cervical radiotherapy (70 Gy). A second treatment with 100 mCi of <sup>131</sup>I confirmed it was a refractory thyroid cancer. Further surgery confirmed a poorly differentiated follicular cancer and 12 cycles of chemotherapy by gemcitabine and oxaliplatin followed. During the 8 years of follow-up, cervical recurrence was stable, but severe episodes of hemoptysis occurred requiring iterative embolization of the bronchial and tracheal arteries. Other lung diseases were excluded. Digital clubbing appeared, which was associated with arthritis, bone pain and inflammatory syndrome. X-rays and magnetic resonance imaging found periosteal apposition in the long bones; bone scintigraphy confirmed the HOA diagnosis. Other causes of arthritis were eliminated. She was treated with colchicine, corticosteroids and nonsteroidal anti-inflammatory drugs, but only the combination of methotrexate and hydroxychloroquine reduced the morphine requirements. Conclusion: HOA is exceptionally associated with thyroid cancer and we raised the hypothesis of the secretion of a circulating factor in a patient with invasive and recurrent follicular thyroid cancer, refractory to radioiodine.

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Lucie Allard Sorbonne Université, GRC n°16, GRC Tumeurs Thyroïdiennes, Unité Thyroïde-Tumeurs Endocrines, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Jérôme Alexandre Denis Sorbonne Université, GRC n°16, GRC Tumeurs Thyroïdiennes, Service de Biochimie Endocrinienne et Oncologique, UF Oncobiologie Cellulaire et Moléculaire, Pitié Salpêtrière, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Gaëlle Godiris Petit Sorbonne Université, GRC n°16, GRC Tumeurs Thyroïdiennes, Service de Chirurgie Générale, Viscérale et Endocrinienne, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Gabrielle Deniziaut Sorbonne Université, GRC n°16, GRC Tumeurs Thyroïdiennes, Service d’Anatomo-Pathologie, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Cécile Ghander Sorbonne Université, GRC n°16, GRC Tumeurs Thyroïdiennes, Unité Thyroïde-Tumeurs Endocrines, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Elise Mathy Sorbonne Université, GRC n°16, GRC Tumeurs Thyroïdiennes, Unité Thyroïde-Tumeurs Endocrines, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Erell Guillerm Sorbonne Université, GRC n°16, GRC Tumeurs Thyroïdiennes, UF d’Onco-Angiogénétique et Génomique des Tumeurs Solides, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Charlotte Lussey-Lepoutre Sorbonne Université, GRC n°16, GRC Tumeurs Thyroïdiennes, Service de Médecine Nucléaire, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Laurence Leenhardt Sorbonne Université, GRC n°16, GRC Tumeurs Thyroïdiennes, Unité Thyroïde-Tumeurs Endocrines, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Camille Buffet Sorbonne Université, GRC n°16, GRC Tumeurs Thyroïdiennes, Unité Thyroïde-Tumeurs Endocrines, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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An 87-year-old woman was referred to our department for a 15 cm right-sided cervical tumor with bleeding and skin ulceration, developed on a 6 cm papillary thyroid carcinoma diagnosed two years earlier. Surprisingly, there were no other compressive symptoms. Unexpectedly, but successfully, total thyroidectomy and neck dissection were performed. There were no poorly differentiated or anaplastic components in the final histological analysis. Impressive dehiscence occurred shortly after surgery and was also successfully managed. Our case highlights the benefit of considering surgery in the context of a tertiary care center even for an apparent massive aggressive cervical mass and despite old age.

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